{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T21:33:22Z","timestamp":1778103202174,"version":"3.51.4"},"reference-count":28,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,2,28]],"date-time":"2019-02-28T00:00:00Z","timestamp":1551312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Vitaflo Ltd as part of PhD grant","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Vitaflo Ltd United Kingdom","award":["001"],"award-info":[{"award-number":["001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Introduction: In phenylketonuria (PKU), evidence suggests that casein glycomacropeptide supplemented with rate-limiting amino acids (CGMP-AA) is associated with better protein utilisation and less blood phenylalanine (Phe) variability. Aim: To study the impact of CGMP-AA on blood Phe variability using 3 different dietary regimens in children with PKU. Methods: This was a 6-week randomised controlled cross-over study comparing CGMP-AA vs. Phe-free l-amino acids (l-AA) assessing blood Phe and tyrosine (Tyr) variability over 24 h in 19 children (7 boys) with PKU, with a median age of 10 years (6\u201316). Subjects were randomised to 3 dietary regimens: (1) R1, CGMP-AA and usual dietary Phe (CGMP + Phe); (2) R2, CGMP-AA \u2212 Phe content of CGMP-AA from usual diet (CGMP \u2212 Phe); and (3) R3, l-AA and usual dietary Phe. Each regimen was administered for 14 days. Over the last 48 h on days 13 and 14, blood spots were collected every 4 h at 08 h, 12 h, 16 h, 20 h, 24 h, and 04 h. Isocaloric intake and the same meal plan and protein substitute dosage at standardised times were maintained when blood spots were collected. Results: Eighteen children completed the study. Median Phe concentrations over 24 h for each group were (range) R1, 290 (30\u2013580), R2, 220 (10\u2013670), R3, 165 (10\u2013640) \u03bcmol\/L. R1 vs. R2 and R1 vs. R3 p &lt; 0.0001; R2 vs. R3 p = 0.0009. There was a significant difference in median Phe at each time point between R1 vs. R2, p = 0.0027 and R1 vs. R3, p &lt; 0.0001, but not between any time points for R2 vs. R3. Tyr was significantly higher in both R1 and R2 [70 (20\u2013240 \u03bcmol\/L] compared to R3 [60 (10\u2013200) \u03bcmol\/L]. In children &lt; 12 years, blood Phe remained in the target range (120\u2013360 \u03bcmol\/L), over 24 h, for 75% of the time in R1, 72% in R2 and 64% in R3; for children aged \u2265 12 years, blood Phe was in target range (120\u2013600 \u03bcmol\/L) in R1 and R2 for 100% of the time, but 64% in R3. Conclusions: The residual Phe in CGMP-AA increased blood Phe concentration in children. CGMP-AA appears to give less blood Phe variability compared to l-AA, but this effect may be masked by the increased blood Phe concentrations associated with its Phe contribution. Reducing dietary Phe intake to compensate for CGMP-AA Phe content may help.<\/jats:p>","DOI":"10.3390\/nu11030520","type":"journal-article","created":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T03:29:21Z","timestamp":1551410961000},"page":"520","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The Effect of Glycomacropeptide versus Amino Acids on Phenylalanine and Tyrosine Variability over 24 Hours in Children with PKU: A Randomized Controlled Trial"],"prefix":"10.3390","volume":"11","author":[{"given":"Anne","family":"Daly","sequence":"first","affiliation":[{"name":"Birmingham Women\u2019s and Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6 NH, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7654-3621","authenticated-orcid":false,"given":"Sharon","family":"Evans","sequence":"additional","affiliation":[{"name":"Birmingham Women\u2019s and Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6 NH, UK"}]},{"given":"Satnam","family":"Chahal","sequence":"additional","affiliation":[{"name":"Birmingham Women\u2019s and Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6 NH, UK"}]},{"given":"Saikat","family":"Santra","sequence":"additional","affiliation":[{"name":"Birmingham Women\u2019s and Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6 NH, UK"}]},{"given":"Alex","family":"Pinto","sequence":"additional","affiliation":[{"name":"Birmingham Women\u2019s and Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6 NH, UK"}]},{"given":"Cerys","family":"Gingell","sequence":"additional","affiliation":[{"name":"Nottingham Queen\u2019s Medical Centre, University Hospital, Derby Road, Nottingham NG7 2UH, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4977-8345","authenticated-orcid":false,"given":"J\u00falio C\u00e9sar","family":"Rocha","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica M\u00e9dica, Centro Hospitalar Universit\u00e1rio do Porto (CHUP), 4099-028 Porto, Portugal"},{"name":"Centro de Refer\u00eancia na \u00e1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUP, 4099-001 Porto, Portugal"},{"name":"Center for Health Technology and Services Research (CINTESIS), 4200-450 Porto, Portugal"}]},{"given":"Francjan","family":"van Spronsen","sequence":"additional","affiliation":[{"name":"Beatrix Children\u2019s Hospital, University Medical Centre of Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"}]},{"given":"Richard","family":"Jackson","sequence":"additional","affiliation":[{"name":"Liverpool University, Brownlow Hill, Liverpool L69 7ZX, UK"}]},{"given":"Anita","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Birmingham Women\u2019s and Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6 NH, UK"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6352919","DOI":"10.1155\/2018\/6352919","article-title":"Comparison of Glycomacropeptide with Phenylalanine Free-Synthetic Amino Acids in Test Meals to PKU Patients: No Significant Differences in Biomarkers, Including Plasma Phe Levels","volume":"2018","author":"Ahring","year":"2018","journal-title":"J. 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